CN101703800B - Nano fiber artificial blood vessel for catalyzing and releasing nitric oxide and preparation method - Google Patents
Nano fiber artificial blood vessel for catalyzing and releasing nitric oxide and preparation method Download PDFInfo
- Publication number
- CN101703800B CN101703800B CN2009102288417A CN200910228841A CN101703800B CN 101703800 B CN101703800 B CN 101703800B CN 2009102288417 A CN2009102288417 A CN 2009102288417A CN 200910228841 A CN200910228841 A CN 200910228841A CN 101703800 B CN101703800 B CN 101703800B
- Authority
- CN
- China
- Prior art keywords
- polyurethane
- blood vessel
- nitric oxide
- artificial blood
- catalyzing
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Images
Landscapes
- Materials For Medical Uses (AREA)
Abstract
本发明公开了一种催化释放一氧化氮的纳米纤维人工血管及制备方法，人工血管由内外两层纳米纤维形成的三维网状无纺膜管结构组成，用下述方法制成：将明胶溶解在冰醋酸中，制溶液；加入肝素钠水溶液，制成纺丝原液，静电纺丝形成纳米纤维无纺膜管；将聚氨酯和铜盐螯合物溶解于四氢呋喃和N，N-二甲基甲酰胺的混合溶剂中，制成聚氨酯纺丝原液，静电纺丝将成形的聚氨酯纤维在收集有纳米纤维无纺膜管的收集辊上继续收集，形成聚氨酯纤维无纺膜管；浸泡于交联剂的水溶液中进行处理。本发明的人工血管在体内外，可长时间催化释放一氧化氮。利于抑制血小板聚集。本发明的方法简单，交联度易于控制。The invention discloses a nanofiber artificial blood vessel that catalyzes the release of nitric oxide and a preparation method thereof. The artificial blood vessel is composed of a three-dimensional net-shaped non-woven membrane tube structure formed by two layers of nanofibers inside and outside, and is made by the following method: dissolving gelatin Prepare a solution in glacial acetic acid; add heparin sodium aqueous solution to make a spinning stock solution, and electrospin to form a nanofiber non-woven film tube; dissolve polyurethane and copper salt chelate in tetrahydrofuran and N,N-dimethylformaldehyde In the mixed solvent of amides, the polyurethane spinning stock solution is made, and the formed polyurethane fibers are collected by electrospinning on the collection roller collecting the nanofiber non-woven membrane tube to form the polyurethane fiber non-woven membrane tube; soaked in the crosslinking agent treatment in an aqueous solution. The artificial blood vessel of the present invention can catalyze and release nitric oxide for a long time inside and outside the body. Helps inhibit platelet aggregation. The method of the invention is simple, and the degree of crosslinking is easy to control.
Description
Technical field
The invention belongs to macromolecular material biomedical applications field, relate to a kind of nano fiber artificial blood vessel and method for preparing.
Background technology
The human vas major injury obtains clinical success from nineteen fifty-two with polyvinyl manufacture of intraocular blood vessel owing to a difficult problem that becomes the puzzlement medical circle from body repair ability difference, and people develop the artificial blood vessel of multiple material successively.The grafting vessel that generally adopts now mainly is to be processed by materials such as terylene, nylon and politef; But these materials are not supported the adhesion and the growth of human endothelial cells; Make the blood vessel of implant into body be difficult to abundant endothelialization, the long adaptation of blood vessel is caused obstacle.Therefore such blood vessel can only be used as the succedaneum of lesion vessels at present, and bore is thicker, and the blood vessel of bore below 6mm finds clinically that because of causing thrombosis easily unimpeded rate is lower, can not satisfy the clinical medicine needs.
The anticoagulation functional molecular that normal endothelial cell comprised has nitric oxide (NO), preceding parathyrine, thrombomodulin, the heparin etc. of splitting.Nitric oxide anticoagulant effectively wherein, but also have the vascular smooth muscle cell curing of inhibition and effects such as bacterial adhesion and promotion wound healing.It is short relatively that the characteristic of the blood vessel dilating of NO also is used for behind the balloon angioplasty treatment, especially its half-life of restenosis, can reduce the hemorrhage side effect of Denging.Existing NO discharges the blood contact material and prepares loaded down with trivial details difficulty, and the blood contact material still has only fixed NO storage capacity, has therefore limited NO and has continued secular release, can not control NO for a long time and discharge, and controllability is relatively poor.
The research contents of engineering blood vessel mainly is to select the natural and synthetic high polymer with good biological performance for use at present; Be built into the nanofiber blood vessel through diverse ways; The final regeneration that realizes from the body blood vessel in back is transplanted in external guiding seed cell propagation, expansion and differentiation in the body.Method of electrostatic spinning can directly form the tubular structure of required bore, and can imitate the The Nomenclature Composition and Structure of Complexes of extracellular matrix, for the adhesion and the growth of cell provides good biotic environment, for regeneration and reconstruction from the body blood vessel provide probability.
Artificial blood vessel's material can be divided into natural biologic material and synthetic material.Adopt natural material to combine, both sides' advantage is carried out complementation and combined, prepare the complex nanometer fibrous tissue engineering blood vessel that can have good mechanical performance and biology performance simultaneously with synthetic material.If the artificial blood vessel of preparation promptly has excellent physical and mechanical performance, the nitric oxide release function is arranged again, will be that people expect.
Summary of the invention
The objective of the invention is to overcome the deficiency that prior art exists, a kind of nano fiber artificial blood vessel of catalyzing and releasing nitric oxide is provided.
Second purpose of the present invention provides a kind of method for preparing of nano fiber artificial blood vessel of catalyzing and releasing nitric oxide.
Technical scheme of the present invention is summarized as follows:
A kind of nano fiber artificial blood vessel of catalyzing and releasing nitric oxide is made up of the three-dimensional netted nonwoven film tubular construction that inside and outside two-layer nanofiber forms, and processes with following method:
(1) with gelatin, collagen, fibroin albumen, elastin laminin or fibrinolysis in glacial acetic acid or water, process mass concentration and be 15%～30% solution;
(2) get the solution 20mL that step (1) prepares; The mass concentration that adds 5mL-10mL is 0.9%～3.0% heparin sodium aqueous solution; Process spinning solution, in the electrospinning device of packing into, adopt electrospinning process; Spinning-nozzle ejection in the electrospinning device and the fiber collecting that is shaped on collecting drum, are formed nanofiber nonwoven film pipe;
(3) be 100 in mass ratio: it is 100 that the ratio of 0.001-5 is dissolved in mass ratio with polyurethane and mantoquita chelate: the oxolane of 25-300 and N; In the mixed solvent of dinethylformamide; Process the polyurethane mass fraction and be 8%～25% polyurethane spinning solution; Pack in the electrospinning device, adopt electrospinning process, spinning-nozzle ejection in the electrospinning device and the polyurethane fiber that is shaped are had in collection on the collecting drum of nanofiber nonwoven film pipe and continue to collect; The axle that forms polyurethane fiber nonwoven film pipe collecting drum is perpendicular to the spinning-nozzle opening direction, and said collecting drum is done uniform rotation along axle;
The nanofiber nonwoven film pipe that (4) will be coated with polyurethane fiber nonwoven film pipe was soaked in after said collecting drum takes off the aqueous solution that mass percentage concentration is the 1%-50% cross-linking agent 1～10 hour or placed and handled in steam 10-24 hour, promptly processed a kind of nano fiber artificial blood vessel of catalyzing and releasing nitric oxide.
Said mantoquita chelate is that cupric salt and the reaction of nitrogenous multidentate ligand obtain.
Said cupric salt is copper chloride, copper nitrate or copper sulfate, and said nitrogenous multidentate ligand is 1,4,7,10-tetraazacyclododecanand, 1,4; 8,11-tetraazacyclododecane tetradecane, 1,4,8,12-tetraazacyclododecane pentadecane or dibenzo [e; K]-2,3,8,9-tetraphenyl-1,4; 7,10-tetraazacyclododecanand-1,3,7,9-tetraene.
Said cross-linking agent be glutaraldehyde, carbodiimides, genipin, divinylsulfone, formaldehyde, Biformyl, malonaldehyde, butanedial, hexandial, heptan dialdehyde, suberic aldehyde, azel aldehyde, decanedial, glucose, glucosan, oxidizing glucose or oxidation glucosan.
Said polyurethane is CorethaneTM;
80A;
90A; Chronoflex AR; ChronoflexCL;
Elast Eon; Cardiothane51 (R); Cardiomat or Avcothane.
A kind of method for preparing of nano fiber artificial blood vessel of catalyzing and releasing nitric oxide, form by following steps:
(1) with gelatin, collagen, fibroin albumen, elastin laminin or fibrinolysis in glacial acetic acid or water, process mass concentration and be 15%～30% solution;
(2) get the solution 20mL that step (1) prepares; The mass concentration that adds 5mL-10mL is 0.9%～3.0% heparin sodium aqueous solution; Process spinning solution, in the electrospinning device of packing into, adopt electrospinning process; Spinning-nozzle ejection in the electrospinning device and the fiber collecting that is shaped on collecting drum, are formed nanofiber nonwoven film pipe;
(3) be 100 in mass ratio: it is 100 that the ratio of 0.001-5 is dissolved in mass ratio with polyurethane and mantoquita chelate: the oxolane of 25-300 and N; In the mixed solvent of dinethylformamide; Process the polyurethane mass fraction and be 8%～25% polyurethane spinning solution; Pack in the electrospinning device; Adopt electrospinning process, spinning-nozzle ejection in the electrospinning device and the polyurethane fiber that is shaped are had in collection on the collecting drum of nanofiber nonwoven film pipe and continue to collect, form polyurethane fiber nonwoven film pipe; The axle of collecting drum is perpendicular to the spinning-nozzle opening direction, and said collecting drum is done uniform rotation along axle;
The nanofiber nonwoven film pipe that (4) will be coated with polyurethane fiber nonwoven film pipe was soaked in after said collecting drum takes off the aqueous solution that mass percentage concentration is the 1%-50% cross-linking agent 1～10 hour or placed and handled in steam 10-24 hour, promptly processed a kind of nano fiber artificial blood vessel of catalyzing and releasing nitric oxide.
Said mantoquita chelate is that cupric salt and the reaction of nitrogenous multidentate ligand obtain.
Said cupric salt is copper chloride, copper nitrate or copper sulfate, and said nitrogenous multidentate ligand is 1,4,7,10-tetraazacyclododecanand, 1,4; 8,11-tetraazacyclododecane tetradecane, 1,4,8,12-tetraazacyclododecane pentadecane or dibenzo [e; K]-2,3,8,9-tetraphenyl-1,4; 7,10-tetraazacyclododecanand-1,3,7,9-tetraene.
Said cross-linking agent be glutaraldehyde, carbodiimides, genipin, divinylsulfone, formaldehyde, Biformyl, malonaldehyde, butanedial, hexandial, heptan dialdehyde, suberic aldehyde, azel aldehyde, decanedial, glucose, glucosan, oxidizing glucose or oxidation glucosan.
Said polyurethane is CorethaneTM;
80A;
90A; Chronoflex AR; ChronoflexCL;
Elast Eon; Cardiothane51 (R); Cardiomat or Avcothane.
Advantage of the present invention:
1. a kind of minute provided by the present invention layer building nano fiber artificial blood vessel, in vivo and in vitro, catalyzing and releasing nitric oxide for a long time.This is beneficial to anticoagulant in the artificial blood vessel.
2. double-layer structure can be controlled nitric oxide and discharge and spread through structural parameters such as the degree of cross linking and fibre diameters.
3. the internal layer of natural polymer formation can avoid the mantoquita chelate in the skin directly to contact with blood.
4. fibre structure can improve specific surface, improves the catalyzing and releasing nitric oxide ability.
5. cross filament film tubular construction processing provided by the present invention is simple, and the degree of cross linking is easy to control.
Description of drawings
Fig. 1 is that the nano fiber artificial blood vessel of catalyzing and releasing nitric oxide is implanted Canis familiaris L. femoral vein bypass surgery photo.
Fig. 2 is the nano fiber artificial blood vessel double-decker photo of catalyzing and releasing nitric oxide; 1 is internal layer among the figure; 2 is that polyurethane is outer.
The specific embodiment
Below in conjunction with specific embodiment the present invention is further described.
Embodiment 1
A kind of nano fiber artificial blood vessel of catalyzing and releasing nitric oxide is made up of the three-dimensional netted nonwoven film tubular construction that inside and outside two-layer nanofiber forms, and processes with following method:
(1) gelatin is dissolved in the glacial acetic acid, processes mass concentration and be 20% solution;
(2) get the solution 20mL that step (1) prepares; The mass concentration that adds 8mL is 2.0% heparin sodium aqueous solution; Process spinning solution, in the electrospinning device of packing into, adopt electrospinning process; Spinning-nozzle ejection in the electrospinning device and the fiber collecting that is shaped on collecting drum, are formed nanofiber nonwoven film pipe;
(3) be that polyurethane CorethaneTM and mantoquita chelate are dissolved in mass ratio is 100: 100 oxolane and N for 100: 0.05 ratio in mass ratio; In the mixed solvent of dinethylformamide; Process the polyurethane mass fraction and be 15% polyurethane spinning solution; Pack in the electrospinning device, adopt electrospinning process, spinning-nozzle ejection in the electrospinning device and the polyurethane fiber that is shaped are had in collection on the collecting drum of nanofiber nonwoven film pipe and continue to collect; The axle that forms polyurethane fiber nonwoven film pipe collecting drum is perpendicular to the spinning-nozzle opening direction, and said collecting drum is done uniform rotation along axle;
The nanofiber nonwoven film pipe that (4) will be coated with polyurethane fiber nonwoven film pipe is soaked in mass percentage concentration after said collecting drum takes off be to handle in 5 hours 30% the glutaraldehyde water solution, promptly processes a kind of nano fiber artificial blood vessel of catalyzing and releasing nitric oxide.
A kind of nano fiber artificial blood vessel of catalyzing and releasing nitric oxide is made up of the three-dimensional netted nonwoven film tubular construction that inside and outside two-layer nanofiber forms, and processes with following method:
(1) gelatin is dissolved in the glacial acetic acid, processes mass concentration and be 20% solution;
(2) get the solution 20mL that step (1) prepares; The mass concentration that adds 8mL is 2.0% heparin sodium aqueous solution; Process spinning solution, in the electrospinning device of packing into, adopt electrospinning process; Spinning-nozzle ejection in the electrospinning device and the fiber collecting that is shaped on collecting drum, are formed nanofiber nonwoven film pipe;
(3) be that polyurethane CorethaneTM and mantoquita chelate are dissolved in mass ratio is 100: 100 oxolane and N for 100: 0.1 ratio in mass ratio; In the mixed solvent of N-NMF; Process the polyurethane mass fraction and be 15% polyurethane spinning solution; Pack in the electrospinning device, adopt electrospinning process, spinning-nozzle ejection in the electrospinning device and the polyurethane fiber that is shaped are had in collection on the collecting drum of nanofiber nonwoven film pipe and continue to collect; The axle that forms polyurethane fiber nonwoven film pipe collecting drum is perpendicular to the spinning-nozzle opening direction, and said collecting drum is done uniform rotation along axle; Said mantoquita chelate is cupric salt copper chloride and nitrogenous multidentate ligand 1,4,7, and the reaction of 10-tetraazacyclododecanand obtains;
The nanofiber nonwoven film pipe that (4) will be coated with polyurethane fiber nonwoven film pipe is soaked in mass percentage concentration after said collecting drum takes off be to handle in 5 hours 30% the glutaraldehyde water solution, promptly processes a kind of nano fiber artificial blood vessel of catalyzing and releasing nitric oxide.
Embodiment 3
A kind of nano fiber artificial blood vessel of catalyzing and releasing nitric oxide is made up of the three-dimensional netted nonwoven film tubular construction that inside and outside two-layer nanofiber forms, and processes with following method:
(1) gelatin is dissolved in the glacial acetic acid, processes mass concentration and be 20% solution;
(2) get the solution 20mL that step (1) prepares; The mass concentration that adds 8mL is 2.0% heparin sodium aqueous solution; Process spinning solution, in the electrospinning device of packing into, adopt electrospinning process; Spinning-nozzle ejection in the electrospinning device and the fiber collecting that is shaped on collecting drum, are formed nanofiber nonwoven film pipe;
(3) be that polyurethane CorethaneTM and mantoquita chelate are dissolved in mass ratio is 100: 100 oxolane and N for 100: 0.2 ratio in mass ratio; In the mixed solvent of dinethylformamide; Process the polyurethane mass fraction and be 15% polyurethane spinning solution; Pack in the electrospinning device, adopt electrospinning process, spinning-nozzle ejection in the electrospinning device and the polyurethane fiber that is shaped are had in collection on the collecting drum of nanofiber nonwoven film pipe and continue to collect; The axle that forms polyurethane fiber nonwoven film pipe collecting drum is perpendicular to the spinning-nozzle opening direction, and said collecting drum is done uniform rotation along axle; Said mantoquita chelate is cupric salt copper chloride and nitrogenous multidentate ligand 1,4,7, and the reaction of 10-tetraazacyclododecanand obtains;
The nanofiber nonwoven film pipe that (4) will be coated with polyurethane fiber nonwoven film pipe is soaked in mass percentage concentration after said collecting drum takes off be to handle in 5 hours 30% the glutaraldehyde water solution, promptly processes a kind of nano fiber artificial blood vessel of catalyzing and releasing nitric oxide.
Embodiment 4
A kind of nano fiber artificial blood vessel of catalyzing and releasing nitric oxide is made up of the three-dimensional netted nonwoven film tubular construction that inside and outside two-layer nanofiber forms, and processes with following method:
(1) with collagenolysis in glacial acetic acid, process mass concentration and be 15% solution;
(2) get the solution 20mL that step (1) prepares; The mass concentration that adds 8mL is 2.0% heparin sodium aqueous solution; Process spinning solution, in the electrospinning device of packing into, adopt electrospinning process; Spinning-nozzle ejection in the electrospinning device and the fiber collecting that is shaped on collecting drum, are formed nanofiber nonwoven film pipe;
(3) be that polyurethane
80A and mantoquita chelate are dissolved in mass ratio is 100: 50 oxolane and N for 100: 5 ratio in mass ratio; In the mixed solvent of dinethylformamide; Process the polyurethane mass fraction and be 15% polyurethane spinning solution; Pack in the electrospinning device; Adopt electrospinning process; Spinning-nozzle ejection in the electrospinning device and the polyurethane fiber that is shaped are had in collection on the collecting drum of nanofiber nonwoven film pipe and continue to collect; The axle that forms polyurethane fiber nonwoven film pipe collecting drum is perpendicular to the spinning-nozzle opening direction, and said collecting drum is done uniform rotation along axle; Said mantoquita chelate is cupric salt copper nitrate and nitrogenous multidentate ligand 1,4,7, and the reaction of 10-tetraazacyclododecanand obtains;
The nanofiber nonwoven film pipe that (4) will be coated with polyurethane fiber nonwoven film pipe is soaked in after said collecting drum takes off the aqueous solution that mass percentage concentration is 1% carbodiimides to be handled in 10 hours, promptly processed a kind of nano fiber artificial blood vessel of catalyzing and releasing nitric oxide.
Embodiment 5
A kind of nano fiber artificial blood vessel of catalyzing and releasing nitric oxide is made up of the three-dimensional netted nonwoven film tubular construction that inside and outside two-layer nanofiber forms, and processes with following method:
(1) fibroin albumen is dissolved in the glacial acetic acid, processes mass concentration and be 30% solution;
(2) get the solution 20mL that step (1) prepares; The mass concentration that adds 5mL is 3.0% heparin sodium aqueous solution; Process spinning solution, in the electrospinning device of packing into, adopt electrospinning process; Spinning-nozzle ejection in the electrospinning device and the fiber collecting that is shaped on collecting drum, are formed nanofiber nonwoven film pipe;
(3) be that polyurethane
90A and mantoquita chelate are dissolved in mass ratio is 100: 200 oxolane and N for 100: 0.001 ratio in mass ratio; In the mixed solvent of dinethylformamide; Process the polyurethane mass fraction and be 8% polyurethane spinning solution; Pack in the electrospinning device; Adopt electrospinning process; Spinning-nozzle ejection in the electrospinning device and the polyurethane fiber that is shaped are had in collection on the collecting drum of nanofiber nonwoven film pipe and continue to collect; The axle that forms polyurethane fiber nonwoven film pipe collecting drum is perpendicular to the spinning-nozzle opening direction, and said collecting drum is done uniform rotation along axle; Said mantoquita chelate is cupric salt copper sulfate and nitrogenous multidentate ligand 1,4,7, and the reaction of 10-tetraazacyclododecanand obtains;
The nanofiber nonwoven film pipe that (4) will be coated with polyurethane fiber nonwoven film pipe is soaked in after said collecting drum takes off the aqueous solution that mass percentage concentration is 50% hexandial to be handled in 1 hour, promptly processed a kind of nano fiber artificial blood vessel of catalyzing and releasing nitric oxide.
Cross-linking agent in the present embodiment also can be selected genipin, divinylsulfone, formaldehyde, Biformyl, malonaldehyde, butanedial, heptan dialdehyde, suberic aldehyde, azel aldehyde, decanedial, glucose, glucosan, oxidizing glucose or oxidation glucosan for use.
Embodiment 6
A kind of nano fiber artificial blood vessel of catalyzing and releasing nitric oxide is made up of the three-dimensional netted nonwoven film tubular construction that inside and outside two-layer nanofiber forms, and processes with following method:
(1) elastin laminin is dissolved in the glacial acetic acid, processes mass concentration and be 25% solution;
(2) get the solution 20mL that step (1) prepares; The mass concentration that adds 10mL is 0.9% heparin sodium aqueous solution; Process spinning solution, in the electrospinning device of packing into, adopt electrospinning process; Spinning-nozzle ejection in the electrospinning device and the fiber collecting that is shaped on collecting drum, are formed nanofiber nonwoven film pipe;
(3) be that polyurethane Chronoflex AR and mantoquita chelate are dissolved in mass ratio is 100: 100 oxolane and N for 100: 0.005 ratio in mass ratio; In the mixed solvent of dinethylformamide; Process the polyurethane mass fraction and be 25% polyurethane spinning solution; Pack in the electrospinning device, adopt electrospinning process, spinning-nozzle ejection in the electrospinning device and the polyurethane fiber that is shaped are had in collection on the collecting drum of nanofiber nonwoven film pipe and continue to collect; The axle that forms polyurethane fiber nonwoven film pipe collecting drum is perpendicular to the spinning-nozzle opening direction, and said collecting drum is done uniform rotation along axle; Said mantoquita chelate is cupric salt copper chloride and nitrogenous multidentate ligand 1,4,8, and the reaction of 11-tetraazacyclododecane tetradecane obtains;
The nanofiber nonwoven film pipe that (4) will be coated with polyurethane fiber nonwoven film pipe takes off to be placed on the steam from said collecting drum and handled in 20 hours, promptly processes a kind of nano fiber artificial blood vessel of catalyzing and releasing nitric oxide.
Embodiment 7
A kind of nano fiber artificial blood vessel of catalyzing and releasing nitric oxide is made up of the three-dimensional netted nonwoven film tubular construction that inside and outside two-layer nanofiber forms, and processes with following method:
(1) with fibrinolysis in glacial acetic acid, process mass concentration and be 20% solution;
(2) get the solution 20mL that step (1) prepares; The mass concentration that adds 8mL is 1.0% heparin sodium aqueous solution; Process spinning solution, in the electrospinning device of packing into, adopt electrospinning process; Spinning-nozzle ejection in the electrospinning device and the fiber collecting that is shaped on collecting drum, are formed nanofiber nonwoven film pipe;
(3) be that polyurethane Chronoflex CL and mantoquita chelate are dissolved in mass ratio is 100: 25 oxolane and N for 100: 0.002 ratio in mass ratio; In the mixed solvent of dinethylformamide; Process the polyurethane mass fraction and be 20% polyurethane spinning solution; Pack in the electrospinning device, adopt electrospinning process, spinning-nozzle ejection in the electrospinning device and the polyurethane fiber that is shaped are had in collection on the collecting drum of nanofiber nonwoven film pipe and continue to collect; The axle that forms polyurethane fiber nonwoven film pipe collecting drum is perpendicular to the spinning-nozzle opening direction, and said collecting drum is done uniform rotation along axle; Said mantoquita chelate is cupric salt copper nitrate and nitrogenous multidentate ligand 1,4,8, and the reaction of 11-tetraazacyclododecane tetradecane obtains;
The nanofiber nonwoven film pipe that (4) will be coated with polyurethane fiber nonwoven film pipe takes off to be placed on the steam from said collecting drum and handled in 10 hours, promptly processes a kind of nano fiber artificial blood vessel of catalyzing and releasing nitric oxide.
Embodiment 8
A kind of nano fiber artificial blood vessel of catalyzing and releasing nitric oxide is made up of the three-dimensional netted nonwoven film tubular construction that inside and outside two-layer nanofiber forms, and processes with following method:
(1) gelatin is dissolved in the glacial acetic acid, processes mass concentration and be 30% solution;
(2) get the solution 20mL that step (1) prepares; The mass concentration that adds 5mL is 3.0% heparin sodium aqueous solution; Process spinning solution, in the electrospinning device of packing into, adopt electrospinning process; Spinning-nozzle ejection in the electrospinning device and the fiber collecting that is shaped on collecting drum, are formed nanofiber nonwoven film pipe;
(3) be that polyurethane
and mantoquita chelate are dissolved in mass ratio is 100: 300 oxolane and N for 100: 0.02 ratio in mass ratio; In the mixed solvent of dinethylformamide; Process the polyurethane mass fraction and be 15% polyurethane spinning solution; Pack in the electrospinning device; Adopt electrospinning process; Spinning-nozzle ejection in the electrospinning device and the polyurethane fiber that is shaped are had in collection on the collecting drum of nanofiber nonwoven film pipe and continue to collect; The axle that forms polyurethane fiber nonwoven film pipe collecting drum is perpendicular to the spinning-nozzle opening direction, and said collecting drum is done uniform rotation along axle; Said mantoquita chelate is cupric salt copper sulfate and nitrogenous multidentate ligand 1,4,8,12-tetraazacyclododecane pentadecane or dibenzo [e, k]-2,3,8, and 9-tetraphenyl-1,4,7,10-tetraazacyclododecanand-1,3,7, the reaction of 9-tetraene obtains;
The nanofiber nonwoven film pipe that (4) will be coated with polyurethane fiber nonwoven film pipe takes off to be placed on the steam from said collecting drum and handled in 24 hours, promptly processes a kind of nano fiber artificial blood vessel of catalyzing and releasing nitric oxide.
Polyurethane in the present embodiment also can be selected Elast Eon, Cardiothane51 (R), Cardiomat or Avcothane for use.
Embodiment 9
The nano fiber artificial blood vessel of a kind of catalyzing and releasing nitric oxide of embodiment 1-3 is to the influence of blood coagulation
Table 1
| Title material | Activated partial thromboplastin time | Thrombin time ` | Prothrombin time |
| Gelatin | 39 seconds | 16 seconds | 12 seconds |
| Embodiment 1 | 130 seconds | 150 seconds | 25 |
| Embodiment | |||
| 2 | 140 seconds | 155 seconds | 23 seconds |
| Embodiment 3 | 135 seconds | 150 seconds | 25 seconds |
The clotting time of gelatin is compared with the clotting time of blank plasma and is changed not quite, and activated partial thromboplastin time, thrombin time, prothrombin time were respectively 39 seconds, and 16 seconds, 12 seconds.And but the clotting time that makes that contains the catalyzing and releasing nitric oxide artificial blood vessel of heparin obviously prolongs.The nano fiber artificial blood vessel of a kind of catalyzing and releasing nitric oxide that table 1 explanation the present invention makes has anticoagulant and activatory function, can improve its blood compatibility.
The external nitric oxide burst size result of the nano fiber artificial blood vessel of table 2 catalyzing and releasing nitric oxide (8 centimetres of length, 5 millimeters of internal diameters, 1 millimeter of wall thickness), 37 degree are in the pH=7.4 phosphate buffer.
Table 2
| | Discharge | 2 hours | Discharge 4 hours | Discharge 24 hours | Discharge 72 hours |
| The artificial blood vessel who does not contain the mantoquita chelate is as reference | 0 | 0 | 0 | 0 | |
| Embodiment 1, mantoquita chelate content 0.05% | 2×10 -8Mole | 3.5×10 -8Mole | 1.5×10 -7Mole | 3.7×10
-7 | |
| Embodiment | |||||
| 2, mantoquita chelate 0.1% | 3×10 -8Mole | 5.4×10 -8Mole | 2.2×10 -7Mole | 5.5×10 -7Mole | |
| Embodiment 3, mantoquita chelate 0.2% | 4×10 -8Mole | 8×10 -8Mole | 4.1×10 -7Mole | 1.0×10 -6Mole |
But the artificial blood vessel that table 2 explanation makes has the catalyzing and releasing nitric oxide function, and its release was 3 days, and this can improve its blood compatibility.
The nano fiber artificial blood vessel of a kind of catalyzing and releasing nitric oxide of the present invention, it is made up of the three-dimensional netted nonwoven film pipe that inside and outside two-layer nanofiber forms.The inner layer material fibre diameter is 50～300nm; The cladding material fibre diameter is 280～800nm.
The technological parameter of each embodiment step (2) electrospinning process: voltage 15kV; Receiving range 10cm, flow rate is 0.3～2.0mL/h, the collecting drum rotating speed is 50～100r/min; Syringe needle is No. 5 pins or No. 6 pins, and the collecting drum uniform rotation is also done axial uniform motion with respect to spinning-nozzle.The internal layer bore is 3-5mm, and length is 15cm, and vascular wall thickness is 0.4mm.
The technological parameter of step (3) electrospinning process: voltage 16～36kV; Receiving range 10～30cm, flow rate is 0.3～2.0mL/h, the collecting drum rotating speed is 50～100r/min; Syringe needle is No. 5 pins or No. 6 pins; On the nonwoven film inner layer film of above-mentioned collecting drum, continue to receive, form the three-dimensional netted nonwoven film of nanofiber outer tube layer, finally make the nano fiber artificial blood vessel of catalyzing and releasing nitric oxide.The bore of the nano fiber artificial blood vessel of said catalyzing and releasing nitric oxide is 3～6mm, and length is 5～15cm, and vascular wall thickness is 0.3～0.7mm; By weight, inner layer material accounts for 20～50%.
Claims (8)
1. the nano fiber artificial blood vessel of a catalyzing and releasing nitric oxide is made up of the three-dimensional netted nonwoven film tubular construction that inside and outside two-layer nanofiber forms, and processes with following method:
(1) with gelatin, collagen, fibroin albumen, elastin laminin or fibrinolysis in glacial acetic acid or water, process mass concentration and be 15%～30% solution;
(2) get the solution 20mL that step (1) prepares; The mass concentration that adds 5mL-10mL is 0.9%～3.0% heparin sodium aqueous solution; Process spinning solution, in the electrospinning device of packing into, adopt electrospinning process; Spinning-nozzle ejection in the electrospinning device and the fiber collecting that is shaped on collecting drum, are formed nanofiber nonwoven film pipe;
(3) be 100 in mass ratio: it is 100 that the ratio of 0.001-5 is dissolved in mass ratio with polyurethane and mantoquita chelate: the oxolane of 25-300 and N; In the mixed solvent of dinethylformamide; Process the polyurethane mass fraction and be 8%～25% polyurethane spinning solution; Pack in the electrospinning device; Adopt electrospinning process, spinning-nozzle ejection in the electrospinning device and the polyurethane fiber that is shaped are had in collection on the collecting drum of nanofiber nonwoven film pipe and continue to collect, form polyurethane fiber nonwoven film pipe; Said mantoquita chelate is that cupric salt and the reaction of nitrogenous multidentate ligand obtain;
The nanofiber nonwoven film pipe that (4) will be coated with polyurethane fiber nonwoven film pipe was soaked in after said collecting drum takes off the aqueous solution that mass percentage concentration is the 1%-50% cross-linking agent 1～10 hour or placed and handled in steam 10-24 hour, promptly processed a kind of nano fiber artificial blood vessel of catalyzing and releasing nitric oxide.
2. the nano fiber artificial blood vessel of a kind of catalyzing and releasing nitric oxide according to claim 1 is characterized in that said cupric salt is copper chloride, copper nitrate or copper sulfate, and said nitrogenous multidentate ligand is 1,4,7,10-tetraazacyclododecanand, 1; 4,8,11-tetraazacyclododecane tetradecane, 1,4,8,12-tetraazacyclododecane pentadecane or dibenzo [e; K]-2,3,8,9-tetraphenyl-1,4; 7,10-tetraazacyclododecanand-1,3,7,9-tetraene.
3. the nano fiber artificial blood vessel of a kind of catalyzing and releasing nitric oxide according to claim 1, it is characterized in that said cross-linking agent be glutaraldehyde, carbodiimides, genipin, divinylsulfone, formaldehyde, Biformyl, malonaldehyde, butanedial, hexandial, heptan dialdehyde, suberic aldehyde, azel aldehyde, decanedial, glucose, glucosan, oxidizing glucose or oxidation glucosan.
4. the nano fiber artificial blood vessel of a kind of catalyzing and releasing nitric oxide according to claim 1 is characterized in that said polyurethane is CorethaneTM,
Chronoflex AR, Chronoflex CL,
Elast Eon, Cardiothane51 (R), Cardiomat or Avcothane.
5. the method for preparing of the nano fiber artificial blood vessel of a catalyzing and releasing nitric oxide is characterized in that being made up of following steps:
(1) with gelatin, collagen, fibroin albumen, elastin laminin or fibrinolysis in glacial acetic acid or water, process mass concentration and be 15%～30% solution;
(2) get the solution 20mL that step (1) prepares; The mass concentration that adds 5mL-10mL is 0.9%～3.0% heparin sodium aqueous solution; Process spinning solution, in the electrospinning device of packing into, adopt electrospinning process; Spinning-nozzle ejection in the electrospinning device and the fiber collecting that is shaped on collecting drum, are formed nanofiber nonwoven film pipe;
(3) be 100 in mass ratio: it is 100 that the ratio of 0.001-5 is dissolved in mass ratio with polyurethane and mantoquita chelate: the oxolane of 25-300 and N; In the mixed solvent of dinethylformamide; Process the polyurethane mass fraction and be 8%～25% polyurethane spinning solution; Pack in the electrospinning device; Adopt electrospinning process, spinning-nozzle ejection in the electrospinning device and the polyurethane fiber that is shaped are had in collection on the collecting drum of nanofiber nonwoven film pipe and continue to collect, form polyurethane fiber nonwoven film pipe; Said mantoquita chelate is that cupric salt and the reaction of nitrogenous multidentate ligand obtain;
The nanofiber nonwoven film pipe that (4) will be coated with polyurethane fiber nonwoven film pipe was soaked in after said collecting drum takes off the aqueous solution that mass percentage concentration is the 1%-50% cross-linking agent 1～10 hour or placed and handled in steam 10-24 hour, promptly processed a kind of nano fiber artificial blood vessel of catalyzing and releasing nitric oxide.
6. the method for preparing of the nano fiber artificial blood vessel of a kind of catalyzing and releasing nitric oxide according to claim 5 is characterized in that said cupric salt is copper chloride, copper nitrate or copper sulfate, and said nitrogenous multidentate ligand is 1,4,7,10-tetraazacyclododecanand, 1; 4,8,11-tetraazacyclododecane tetradecane, 1,4,8,12-tetraazacyclododecane pentadecane or dibenzo [e; K]-2,3,8,9-tetraphenyl-1,4; 7,10-tetraazacyclododecanand-1,3,7,9-tetraene.
7. the method for preparing of the nano fiber artificial blood vessel of a kind of catalyzing and releasing nitric oxide according to claim 5, it is characterized in that said cross-linking agent be glutaraldehyde, carbodiimides, genipin, divinylsulfone, formaldehyde, Biformyl, malonaldehyde, butanedial, hexandial, heptan dialdehyde, suberic aldehyde, azel aldehyde, decanedial, glucose, glucosan, oxidizing glucose or oxidation glucosan.
8. the method for preparing of the nano fiber artificial blood vessel of a kind of catalyzing and releasing nitric oxide according to claim 5 is characterized in that said polyurethane is CorethaneTM,
Chronoflex AR, Chronoflex CL,
Elast Eon, Cardiothane51 (R), Cardiomat or Avcothane.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009102288417A CN101703800B (en) | 2009-11-27 | 2009-11-27 | Nano fiber artificial blood vessel for catalyzing and releasing nitric oxide and preparation method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009102288417A CN101703800B (en) | 2009-11-27 | 2009-11-27 | Nano fiber artificial blood vessel for catalyzing and releasing nitric oxide and preparation method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101703800A CN101703800A (en) | 2010-05-12 |
| CN101703800B true CN101703800B (en) | 2012-10-31 |
Family
ID=42374095
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009102288417A Expired - Fee Related CN101703800B (en) | 2009-11-27 | 2009-11-27 | Nano fiber artificial blood vessel for catalyzing and releasing nitric oxide and preparation method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101703800B (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105963778B (en) * | 2016-06-07 | 2019-03-15 | 扬州市第一人民医院 | Multi-structure artificial blood vessel stent with inner layer releasing NO gas and preparation method thereof |
| CN107789666A (en) * | 2016-08-30 | 2018-03-13 | 北京航空航天大学 | A kind of inwall micro-patterning small-caliber artificial blood vessel |
| KR20200108862A (en) * | 2018-01-11 | 2020-09-21 | 엠피세마 솔루션스 비브이 | Compositions and methods for the treatment of emphysema and other forms of COPD |
| CN109651586A (en) * | 2018-12-19 | 2019-04-19 | 中国科学院长春应用化学研究所 | The polyurethane containing selenium and the preparation method and application thereof of stable, controllable nitric oxide releasing |
| CN114681687B (en) * | 2022-03-25 | 2022-12-02 | 河北科技大学 | Anticoagulant nanofiber |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1961974A (en) * | 2005-11-09 | 2007-05-16 | 中国科学院化学研究所 | Nano copolymer fibrous membrane material capable of being biodegraded and absorbed and preparation process and use thereof |
| WO2008000198A2 (en) * | 2006-06-30 | 2008-01-03 | Elmarco, S.R.O. | Formation comprising at least one nanofibre layer and method of nanofibre layer production |
| CN101156962A (en) * | 2007-10-19 | 2008-04-09 | 东华大学 | Preparation method of composite nanofibrous tissue repair scaffold containing collagen |
-
2009
- 2009-11-27 CN CN2009102288417A patent/CN101703800B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1961974A (en) * | 2005-11-09 | 2007-05-16 | 中国科学院化学研究所 | Nano copolymer fibrous membrane material capable of being biodegraded and absorbed and preparation process and use thereof |
| WO2008000198A2 (en) * | 2006-06-30 | 2008-01-03 | Elmarco, S.R.O. | Formation comprising at least one nanofibre layer and method of nanofibre layer production |
| CN101156962A (en) * | 2007-10-19 | 2008-04-09 | 东华大学 | Preparation method of composite nanofibrous tissue repair scaffold containing collagen |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101703800A (en) | 2010-05-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Chen et al. | Three-dimensional layered nanofiber sponge with in situ grown silver-metal organic framework for enhancing wound healing | |
| CN101708344B (en) | Nanofiber vascular prostheses and preparation method | |
| CN101214393B (en) | Nano fibrous tissue engineering blood vessel and preparation thereof | |
| CN101703800B (en) | Nano fiber artificial blood vessel for catalyzing and releasing nitric oxide and preparation method | |
| CN106075596B (en) | Preparation technology of three-layer artificial blood vessel | |
| Sindhu et al. | Medical applications of cellulose and its derivatives: present and future | |
| US9662233B2 (en) | Antithrombotic artificial blood vessel | |
| US9683216B2 (en) | Method for preparation of artificial blood vessel using tube-type porous biodegradable scaffold having a double-layered structure and stem cell, and artificial blood vessel made by the same | |
| CN102085393A (en) | Biodegradable nerve conduit with bilayer structure and preparation method thereof | |
| CN113648114B (en) | Coated stent and preparation method thereof | |
| CN102277737A (en) | Preparation method and application of polycaprolactone/natural high-molecular composite porous scaffold | |
| CN102961783A (en) | Construction method of anticoagulant artificial blood vessel scaffold material | |
| EP3315147A1 (en) | Hybrid scaffold suitable for regenerating tissues and production process | |
| CN101385872A (en) | A method for preparing absorbable biomaterial artificial vascular stent by electrospinning | |
| CN108478843B (en) | Medical dressing with copper-containing coating and preparation method thereof | |
| CN101703796A (en) | Nano fibre artificial vascular graft modifying internal layer and preparation method thereof | |
| CN104826169A (en) | New artificial blood vessel | |
| CN101703802B (en) | Nano fiber artificial blood vessel for catalyzing endogenous NO precursor to release NO and preparation method | |
| CN115990293A (en) | Preparation method of medical multilayer self-supporting drug-loaded shell-core structure nanofiber tube | |
| CN108379669B (en) | Medical catheter with copper-containing coating and preparation method thereof | |
| CN103861158A (en) | Preparation method of silk fibroin and sulfated silk fibroin composite tubular scaffold | |
| JP2007268239A (en) | Artificial blood vessel | |
| Wang et al. | Self-assembled photothermal conversion shell coating on the surface of CA/SP for photothermal bacteriostasis and rapid wound healing | |
| US10987501B2 (en) | Cell impregnated sleeve for paracrine and other factor production | |
| CN116440333B (en) | An absorbable vascular stent coating that promotes endothelialization and its preparation method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20201120 Address after: Group 22, zhangsha village, Shizong Town, Tongzhou District, Nantong City, Jiangsu Province Patentee after: Nantong Shuanghui medical equipment Technology Co.,Ltd. Address before: 300072 Tianjin City, Nankai District Wei Jin Road No. 92 Patentee before: Tianjin University |
|
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20121031 |